Catalytic Enantioselective Cyclization/Cross-Coupling with Alkyl Electrophiles

As
part of our ongoing effort to expand the scope of cross-coupling
reactions of alkyl electrophiles, we have pursued a strategy wherein
the nucleophilic coupling partner includes a pendant olefin; after
transmetalation by such a substrate, if β-migratory insertion
proceeds faster than direct cross-coupling, an additional carbon–carbon
bond and stereocenter can be formed. With the aid of a nickel/diamine
catalyst (both components are commercially available), we have established
the viability of this approach for the catalytic asymmetric synthesis
of 2,3-dihydro­benzo­furans and indanes. Furthermore, we
have applied this new method to the construction of the dihydrobenzofuran
core of fasiglifam, as well as to a cross-coupling with a racemic
alkyl electrophile; in the latter process, the chiral catalyst controls
two stereocenters, one that is newly generated in a β-migratory
insertion and one that begins as a mixture of enantiomers.